55

ESP

E

Poster

presented at:

Ovotesticular Disorder of Sex Development (OT- DSD) among Egyptian DSD patients

Mona Mekkawy, Alaa K Kamel, Amal M Mohamed and *Inas MazenNational research Centre. Human cytogenetics dept., *Clinical genetics dept.

Patients:

Among 540 DSD patients studied over a period of 5 years (2010-2015)who were referred to the Clinical Genetics and endocrinology Clinic, NRC,Cairo, Egypt, we report 8 patients with OT-DSD, The patients constituted6% of the patients presenting with ambiguous genitalia and 1.5 % of allpatients.Seven patients presented with ambiguous genitalia, One male patientpresented with pubertal breast development.OT-DSD pathological diagnosis was confirmed in all patients.

Methods:

Detailed clinical examination Anthropometric measurements ,Hormonal assayImaging examinationsChromosomal analysis and Fluorescence in situ hybridization (FISH) Laparoscopy, laparotomy and gonadal biopsy with gonadal histopathological examination. ,FISH on gonadal tissue cells

Patient 1 2 3 4 5 6 7 8

Sex of rearing Female Female Male Female Female changed to a male Male Male Male

Age (year:month)

13:00 00:09 11:08 3 years 12:00 25:10 00:06 03:06

Laparoscopy Testis like gonad

(inguinal region)/ovary,

Hypoplasic uterus

Dysgenetic testis

(inguinal region)/ovary, Left

fallopian tube, uterus.

A uterus and a left gonad, right

scrotal swelling.

Prepubertal uterus and

bilateral gonads.

Prepubertal uterus and no

gonadal tissue visualized.

Right side Fallopian

tube and a small cystic

ovary, uterus, left side

gonad appeared as

testes

Normal size left

testis with

minimal

hydrocele, Right

gonad not

detected.

A uterus and two

gonads

Pathology Right: dysgenetic testis,

Left: ovary with

some follicular activity

Right: Dysgenetic

testis, left: ovotestis

Both testicular and ovarian tissues

within the left gonad.

Rt scrotal epididymal cyst.

Bilateral ovotestis.

testicular

Left dysgenetic testis, right

ovotestis

testicular biopsy:

testicular tissue

showing small tubules,

lined by sertoli cells.

left testicular

tissue, right

ovotestis

Both testicular and

ovarian tissues in

the left gonad., Rt.

Testicular tissues

Cytogenetic results

45,X [60]/46,X, idic(Y)

(p11.32)[40].

ish idic(Y)(p11.32) (wcpY+,

Xp/Yp-, SRY+, DYZ3++)

45,X[75]/46,X, idic(Y)

(p11.32)[15]/ 47,X,idic(Y)

(p11.32)x2[4]/ 46,XY[6]

ish idic(Y)(p11.32) (wcpY+,

Xp/Yp-,

SRY+, DYZ3++)

mos

46,X,dic(X;Y)(p22.33;p11.32)[65]/45

,X[23]/45,dic(X;Y)

(p22.33;p11.32)[12].

ish: t(X;Y)(p22.33;p11.32)(DXZ1+/

DYZ3+, KAL+, SHOX–, Xp–/Yp–,

SRY+).

46,XX

ish: (DXZ1++/DYZ3-, SRY-

)

46,XX

ish: (DXZ1++/DYZ3-, SRY-)

46,XX

ish: (DXZ1++/ SRY-)

46,XY[70]/

46,XX[30]

46,XX

ish: (DXZ1++/DYZ3-, SRY-)

FISH on gonadal tissue

nuc ish

X/Ycen(DXZ1x2,DYZ3x1)(DXZ1

con DYZ3x1) [67]/

(DXZ1x1)[23]/(DXZ1x1,DYZ3x1)(D

XZ1 con DYZ3) [10]

nuc ish X/Ycen

(DXZ1x1)[35]/ (DXZ1x2)

[55]/ (DXZ1x1,DYZ3x1)

[10]

nuc ish Xcen(DXZ1x2),

Yp11.32 (SRY-)

a) FISH analysis showing two hybridization

signals for the Y centromere

probe (DYZ3); (b) one signal for LSI SRY probe

a) FISH analysis on blood metaphase and interphase cells of patients 4 showing two

hybridization signals for X centromeres (DXZ1).

b) FISH on gonadal tissue cells showing three cell lines revealing: two hybridization signals

for the X centromere, one X centromeric signal and hybridization signals for both CEP X

and CEP Y.

a) GTG partial karyotype for the normal and derivative X

chromosomes.

b) FISH showing a hybridization signal for the SRY gene

probe on the translocation chromosome

a b

Objectives

Clinical, histopathological and and Cytogenetic studying of this rare form of Disorders of sex development (DSD) among Egyptian patients.

Introduction

Ovotesticular disorder of sex development (OT-DSD) is a rare disorder ofsexual differentiation characterized by the presence of both testicular andovarian tissues in the gonads of the same individual. The incidence of OT-DSD ranges from 3% to 10% of all DSD. Patients usually prese,nt at birthwith ambiguous genitalia, and the majority show a 46,XX karyotype, withabsence of the SRY sequence (Matsui et al., 2011; Khadilkar et al., 2015)The etiology may be due to 46,XX/46,XY chimerism as a result offertilization of the ovum and the polar body or tetragametic fusion,mosaicism with various combinations (46,XX/47,XXY, 45X/46,XY) (Paula etal., 2015) or mutations of autosomal or sex chromosome genes involved inthe testis-determining pathway.

Results

References:● Khadilkar KS, Budyal SR, Kasaliwal R, Sathe PA, Kandalkar B, Sanghvi BV, Parelkar SV, Lila AR, Bandgar T, Shah NS. (2015) OVOTESTICULAR DISORDER OF SEX DEVELOPMENT: A SINGLE-CENTER EXPERIENCE .Endocr

Pract.21:770-6.

● Matsui F, Shimada K, Matsumoto F, Itesako T, Nara K, Ida S, Nakayama M. 2011 Long-term outcome of ovotesticular disorder of sex development: a single center experience.

Int J Urol. 18:231-6.

● Paula GB, Ribeiro Andrade JG, Guaragna-Filho G, Sewaybricker LE, Miranda ML, Maciel-Guerra AT, Guerra-Júnior G. (2015) Ovotesticular disorder of sex development with unusual karyotype: patient report. J Pediatr Endocrinol Metab. 28:677-

80.

Conclusions: OT DSD should be considered as one of the differential diagnoses in cases of ambiguous genitalia with non palpable or asymmetrical gonads, pubertal gynecomastia,

and cyclical hematuria, irrespective of the karyotype or internal genitalia.

Gonadal biopsy is important in to establish diagnosing cases of sex chromosome mosaicism.

Chromosome studies carried out on peripheral lymphocytes do not always reflect the proportion of cell lines in the gonads.

416--P2Mona Mekkawy DOI: 10.3252/pso.eu.55ESPE.2016

Gonads & DSD